Compoint M, Boiteux C, Huetz P, Ramseyer C, Girardet C
Laboratoire de Physique Moléculaire, UMR CNRS 6624, Université de Franche-Comté, F-25030 Besançon Cedex, France.
Phys Chem Chem Phys. 2005 Dec 21;7(24):4138-45. doi: 10.1039/b508281a. Epub 2005 Oct 6.
Molecular dynamics simulations supported by electrostatic calculations have been conducted on the KcsA channel to determine the role of water molecules in the pore. Starting from the X-ray structure of the KcsA channel in its closed state at 2.0 angstroms resolution, the opening of the pore towards a conformation built on the basis of EPR results is studied. We show that water molecules act as a structural element for the K+ ions inside the filter and the hydrophobic cavity of the channel. In the filter, water tends to enhance the depth of the wells occupied by the K+ ions, while in the cavity there is a strong correlation between the water molecules and the cavity ion. As a consequence, the protein remains very stable in the presence of three K+ ions in the selectivity filter and one in the cavity. The analysis of the dynamics of water molecules in the cavity reveals preferred orientations of the dipoles along the pore axis, and a correlated behavior between this dipole orientation and the displacement of the K+ ion during the gating process.
在静电计算的支持下，对KcsA通道进行了分子动力学模拟，以确定水分子在孔道中的作用。从分辨率为2.0埃的处于关闭状态的KcsA通道的X射线结构出发，研究了孔道向基于电子顺磁共振结果构建的构象的开放过程。我们表明，水分子是通道过滤器内部和疏水腔内钾离子的结构元件。在过滤器中，水倾向于加深钾离子占据的阱的深度，而在腔内，水分子与腔内离子之间存在很强的相关性。因此，在选择性过滤器中有三个钾离子且腔内有一个钾离子的情况下，蛋白质保持非常稳定。对腔内水分子动力学的分析揭示了偶极子沿孔轴的优先取向，以及在门控过程中这种偶极子取向与钾离子位移之间的相关行为。
